Epilepsy Flashcards
define convulsion
Sudden attack of involuntary muscular contractions and relaxations.
define seizure
Abnormal central nervous system electrical activity
define epilepsy
A group of recurrent disorders of cerebral function characterised by both seizures and convulsions.
Epidemiology: when does epilepsy present
> usually in childhood or adolescence but may occur for the first time at any age
Epidemiology: what population of people suffer from a single seizure at some time
5%
Epidemiology: what % of people have epilepsy
0.5 - 1%
Epidemiology: what % of the population are well controlled with drugs and partially resistant to drug treatment
> 70% well controlled
> 30% are partially resistant to drug treatment
what is it called when you’re resistant to drug treatments
INTRACTABLE (pharmaco-resistant) EPILEPSY
describe some clinical features of seizures
> > not life threatening
brain almost always stops seizures on its own
breathing may cease for a few secs
its usually painless
what are the 2 broad classifications of seizures based on
nature of the seizures rather than the presence or absence of an underlying cause
what are the 2 classifications of seizures
- Focal seizures (partial seizures
- Generalised seizures
how many subtypes are in each broad categories
- focal seizures : 3
- generalised seizures: 6
which brain section does partial (Focal seizures) occur?
Excessive electrical activity in one cerebral hemisphere -> Affects only part of the body.
what are the 3 subtypes of partial (focus) seizures
simple partial
complex partial
secondary generalised seizures
describe simple partial seizures
> > Patients has sudden clonic jerking of one extremity lasting 60-90 seconds.
> > Patients is completely aware of the attack and can describe it in detail –> Key feature: preservation of consciousness.
describe complex partial seizures
> > Localised onset, but discharge can spread
> > Loss of awareness at seizure onset :Impairment of consciousness, although consciousness is not fully lost
> > Typically originate in frontal or temporal lobes (e.g. Temporal lobe epilepsy) making it Difficult to treat with drugs so Surgical resection is used.
describe secondary generalised seizures
> > Focal seizures -> generalised Seizures.
> > Often preceded by an AURA or warning sign -> the senses of taste, smell or vision are heightened,
what is generalised seizures
Excessive electrical activity in both cerebral hemispheres
where in the brain does generalised seizures originate
thalamus or brainstem
where in the body do generalised seizures affect
> the entire body
loss of consciousness is common
what are the 6 subtypes of generalised seizures
> myoclonic
atonic
tonic seizures
clonic seizures
tonic - clonic (glnd mal ) seizures
absence (petit mal)
status epilepticus
describe myoclonic seizures
Brief shock-like muscle jerks generalized or restricted to part of one extremity
Describe atonic seizures
sudden loss of muscle tone
Describe tonic seizures
sudden stiffening of the body, arms of legs
Describe clonic seizures
rhythmic jerking movements of the arms and legs without a tonic component
describe tonic - clonic seizures
Tonic phase followed by clonic phase
what is grand mal seizure also called
tonic - clonic seizures
describe absence seizure
- rapid and brief loss of consciousness
- can include the blinkng of the eye lids or lip movements
which group of people is absence seizures most common in
young children
what is absence seizures also known as
petit mal
describe features status epilepticus
> seizure lasting longer than 30 min or 3 seizures without a normal period in between
> may be fatal
> emergency intervention requird
list the 7 epileptic syndromes associated with neurological conditions
> west syndrome
> lennox - gastaut syndrome
> juvenile myoclonic epilepsy
> Doose syndrome
> Dravet syndrome
> Benign neonatal convulsions
> Temporal lobe epilepsy.
Lennox, Doose and Dravet are Juveniles in West Temporal Benign
what is the neurobiology explanation of epilepsy of the 19th century neurologist
a sudden excessive disorderly discharge of CEREBRAL neurons
who was the 19th century neurologist
hughlings jackson
what is the recent neurobiology explanation of epilepsy
> > a central role for the excitatory neurotransmiter glutamate (increased in epilepsy)
> > inhibitory gamma amino butyric acid (GABA) (decreased)
what are the causes of epilepsy
> genetic (autosomal dominant genes)
congenital defects (8%)
severe head trauma
ischemic injury , tumor
drug abuse
unknown (65%)
what are antiepileptic drug (AED)
a drug which decreases the frequency and/or severity of seizures in people with epilepsy
> it treats symptoms not cure
do AED prevent development of epilepsy individuals with acquired risk for seizures (e.g after head trauma, stroke)
NO
What happens when patient do not respond to drug therapy
surgery
what is the goal of drug therapy
maximise quality of life by eliminating seizures (or diminish seizure frequency) while minimizing adverse drug effects
what are the 3 mechanism of actions of AED
- Inhibition of voltage-gated Na+ channels to slow neuron firing.
- Enhancement of the inhibitory effects of the neurotransmitter GABA.
3.Inhibition of calcium channels.
do some drugs fall into more than 1 of these categories of MOA
YES, and some drugs dont fall into any of these categories
which AED is the oldest and what year
Phenytoin 1938
what is Phenytoin
A non sedative AED
describe the MOA of phenytoin
- Use-dependent block of sodium ion channels
- Prolongs their inactive state -> prevents further action potential generation
- Reduces the synaptic release of glutamate and enhances the release of GABA
which seizure is phenytoin not effective
absence
why is drug monitoring essential for phenytoin
> > it is highly bound to plasma protein s( about 90%)
> > there is a non linear relationship between dose and plasma conc
> > therefore extreme variation in plasma conc
> > this could lead to toxic effects
list the adverse effects of phenytoin
- Nystagamus (involuntary and jerky repetitive movements of the eyeballs) occur early in treatment
- .Gingival hyperplasia = increase in the size of the gingiva (gums)
- Hirsutism = excessive body hair
- Diplopia = double vision (dose related)
5.Ataxia = lack of voluntary coordination of muscle movements (dose related)
6.Sedation = dose related
foetal abnormalities when taken by the mother during pregnancy
What is carbamazepine structurally related to
Tricyclic antidepressants
what are the MOA of carbamazepine
- Inhibition of voltage-gated Na+ channels to slow neuron firing.
- Enhancement of the inhibitory effects of the neurotransmitter GABA.
When is carbamazepine chosen
partial and generalised seizure
When is carbamazepine not effective
absence seizures
which conditions is carbamazepine also effective in
trigeminal neuralgias
mania
what are the main side effects of carbamazepine
> sedation
> ataxia = a term for a group of disorders that affect co-ordination, balance and speech
> mental disturbances
> water retention
what is Oxcarbazepine
- a drug that is structurally and functionally related to carbamazepine but follows a different metabolic pathway so its better tolerated and has more advantages
what are the MOA of sodium valproate
- Suppress repetitive neuronal firing through inhibition of voltage-sensitive sodium ion channels
- Suppresses thalamic excitability by inhibiting transient low threshold calcium ion channels
- Enhances GABA in CNS by inhibiting the catabolic enzyme GABA transaminase.
which seizure sodium valproate the drug of choice
absences seizures
is sodium valproate effective in al forms of epilepsy
YES
what are the side effects of sodium valproate included in jerom’s slides
alopecia
liver damage (rare )
teratogenic (affects fetus )
what are the common side effects of soidum valproate in the bnf
Abdominal pain; agitation; alopecia (regrowth may be curly); anaemia; behaviour abnormal; concentration impaired; confusion; deafness; diarrhoea; drowsiness; haemorrhage; hallucination; headache; hepatic disorders; hypersensitivity; hyponatraemia; memory loss; menstrual cycle irregularities; movement disorders; nail disorder; nausea; nystagmus; oral disorders; seizures; stupor; thrombocytopenia; tremor; urinary disorders; vomiting; weight increased
which seizure is ethosuximide the drug of choice
absences seizures
what is the MOA of ethosuximide
it reduces low threshold calcium ion currents ( T- type Ca2+ channels#) in thalamic neurons
what are the side effects of ethosuximide ( according to slides)
nausea and anorexia
what are the bnf side effects of ethosuximide not required to know
Aggression; agranulocytosis; appetite decreased; blood disorder; bone marrow disorders; concentration impaired; depression; diarrhoea; dizziness; drowsiness; erythema nodosum; fatigue; gastrointestinal discomfort; generalised tonic-clonic seizure; headache; hiccups; leucopenia; libido increased; lupus-like syndrome; mood altered; movement disorders; nausea; nephrotic syndrome; oral disorders; psychosis; rash; sleep disorders; Stevens-Johnson syndrome; suicidal behaviours; vaginal haemorrhage; vision disorders; vomiting; weight decreased
which seizure is GABAPENTIN the drug of choice
partial seizures
what is the MOA of gabapentin
- Blocks glutamate stimulated Ca ion channels
- inhibits depolarisation induced calcium influx at nerve terminals which decreases glutamate release
what are the side effects of gabapentin ( according to slides
nausea and sedation
which seizures is LAMOTRIGINE the drug of choice
partial seizures
tonic- clonic seizures
absences seizures
what is the MOA of LAMOTRIGINE
- inhibits release of glutamate
- suppresses repetitive neuronal firing by inhibition of voltage sensitive sodium ion channels
what are the side effects of lamotrigine
nausea , sedation, ataxia, skin rashes
which seizure is TIAGABINE the drug o choice
partial seizures
what is the MOA of tiagabine
inhibits the GABA transporter responsible for removing extracellular levels of GABA
therefore:
- increased levels of GABA in synapses
- increased inhibitory transmission
what are the side effects of tiagabine
nausea , sedation , ataxia
which seizure is LEVETIRACETAM the drug of choice
partial seizures
what is the MOA of Levetiracetam
binds to synaptic vesicular protein SV2A and this alters synaptic neurotransmitter release
what are the side effects of levetiracetam
- somnolence : sleepiness
- asthenia : abnormal physical weakness or lack of energy
- Dizziness
which seizures is TOPIRAMATE the drug of choice
> Effective against partial and generalised tonic-clonic seizures and absence seizures
> Broad effectiveness against a range of epilepsy syndromes (Lennox Gastaut; West’s syndrome
what condition is topiramate also approved for
migraine headaches
how is topiramate different from other AEDs
it has a monosaccharide structure
what is the MOA of topiramate
- blocks voltage gated sodium channel s
- potentiated the effects of GABA (similar to benzodiazepines but has distinct binding site on GABAA receptors)
- depresses excitatory effect of kainate on glutamate receptor
what are the side effects of topiramate according to slides
- Somnolence,
- fatigue,
- dizziness,
- paraesthesia
-nervousness, - confusion
-Acute myopia (near-sightedness)
-glaucoma> rare, but requires immediate withdrawal
which seizure is VIGABATRIN the drug of choice
partial seizures
what is the MOA of vigabatrin
Irreversible inhibitor of the enzyme GABA aminotransferase, the enzyme that degrades GABA
this causes:
> Increased levels of GABA released at synaptic sites
> Enhanced neuronal inhibition
what are the side effects of vigabatrin
Drowsiness
Dizziness
Weight gain
what is cannabidiol ~(CBD)
major component of the cannabis sativa plant
does CBD have psychoactive properties
NO, it’s THC that has that
what are the methods of retrieving CBD
- synthesized to make synthetic cbd
- Plant derived
which 2 boards approve cbd
FDA
EMA
which syndrome is CBD used in
- Dravet syndrome
- lennox - gastaut syndrome
what is the first line treatment of focal seziures
Carbamazepine
lamotrigine
what is the second line treatment of focal seizures
levetiracetam
oxcarbazepine
sodium valproate
what are the cautions for focal seizures
be aware of the potential effect of sodium valproate in pregnancy
what is the adjunctive treatment (if firt and second line is not effective or tolerated)
carbamazepine, clobazam, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, sodium valproate, topiramate
what is the action if adjunctive treatment is not effective or tolerated
consider referral to tertiary epilepsy services (where other AEDs may be tried)
such as :
eslicarbazepine acetate, lacosamide, phenobarbital, phenytoin, pregabalin, tiagabine, vigabatrin and zonisamide
what is the first line treatment for tonic clonic seizures
sodium valproate
lamotrigine (if sodium valproate is not suitable)
what are the cautions to be aware of for the first line treatment of tonic clonic
be aware of potential effect of sodium valproate in pregnancy.
If the person has myoclonic seizures or may have juvenile myoclonic epilepsy lamotrigine may worsen myoclonic seizures
what is the second line treatment for tonic clonic seizures
carbamazepine, oxcarbazepine
what is the second line treatment of tonic clonic seizures
carbamazepine
oxcarbazepine
what are cautions of second line treatment of tonic clonic seizures
may worsen myoclonic or absence siezures
what is the adjunctive treatment (if first or second line is not effective or tolerated) of tonic clonic seizures
lamotrigine, levetiracetam, sodium valproate, topiramate
which drugs do you not offer when the patient also has absences or myoclonic seizures or juvenile myoclonic epilepsy
carbamazepine, gabapentin, oxcarbazepine, phenytoin, pregabalin, tiagabine or vigabatrin
what is the first line treatment of absence seizures
ethosuximide, sodium valproate (offer first if additional tonic clonic seizures are likely
when do you offer sodium valproate first in absence seizures
if patient may have tonic clonic seizures
what is the second line treatment of absence seizures
lamotrigine
what is the adjunctive treatment of absence seizures
consider a combination of ethosuximide, lamotrigine or sodium valproate.
which drugs do you avoid in a patient with absence siezures
carbamazepine, gabapentin, oxcarbazepine, phenytoin, pregabalin, tiagabine, vigabatrin
what is the next step if adjunctive treatment is not effective or tolerated in absence seizure
consider referral to tertiary epilepsy services (where other AEDs may be tried)
what is the first line treatment of myoclonic seizures
sodium valproate
what is the caution for the first line treatment of myoclonic seizure
aware of potential effects in pregnancy
what is the second line treatment of myoclonic seizure
levetiracetam, topiramate
what is the caution of topiramate in use of myoclonic seizure
has poorer side effects than levetiracetam and sodium valproate
what is the adjunctive treatment for myoclonic seizures
levetiracetam, sodium valproate, topiramate
what is the next step if adjunctive treatment is not effective or tolerated in myoclonic seizure
consider referral to tertiary epilepsy services (where other AEDs may be tried)
such as: Clobazam, clonazepam, piracetam, zonisamide
which medications do you not offer in patients with myoclonic seizures
carbamazepine, gabapentin, oxcarbazepine, phenytoin, pregabalin, tiagabine or vigabatrin
what is the first line treatment of tonic and atonic seizures
sodium valproate
what is the second line treatment of tonic and atonic seizures
none
what is the adjunctive treatment of tonic and atonic seizures
lamotrigine
what is the next step if adjunctive treatment is not effective or tolerated in tonic and atonic seizures
consider referral to tertiary epilepsy services (where other AEDs may be tried):
such as: rufinamide, topiramate
which medications do you not offer in patients with tonic and atonic seizures
carbamazepine, gabapentin, oxcarbazepine, pregabalin, tiagabine or vigabatrin
